title: Human mesenchymal stem cells are susceptible to lysis by CD8(+) T cells and NK cells.
abstract: There is growing interest in the use of mesenchymal stem cells (MSCs) to improve the outcome of organ transplantation. The immunogenicity of MSCs is, however, unclear and is important for the efficacy of MSC therapy and for potential sensitization against donor antigens. We investigated  the susceptibility of autologous and allogeneic MSCs for lysis by CD8(+) T-lymphocytes and NK cells in a kidney transplant setting. MSCs were derived from adipose tissue of human kidney donors and were CD90(+), CD105(+), CD166(+), and HLA class I(+).  They showed differentiation ability and immunosuppressive capacity. Lysis of MSCs by peripheral blood mononuclear cells (PBMCs), FACS-sorted CD8(+) T cells, and NK cells was measured by europium release assay. Allogeneic MSCs were susceptible for lysis by cytotoxic CD8(+)  T cells and NK cells, while autologous MSCs were lysed by NK cells only. NK cell-mediated lysis was inversely correlated with the expression of HLA class I on MSCs. Lysis of autologous MSCs was not dependent on culturing of MSCs in FBS, and MSCs in suspension as well as adherent to plastic  were lysed by NK cells. Pretransplant recipient PBMCs did not lyse donor MSCs, but PBMCs isolated 3, 6, and 12 months after transplantation showed increasing lysing ability. After 12 months, CD8(+) T-cell-mediated lysis of donor MSCs persisted, indicating there was no evidence for  desensitization against donor MSCs. Lysis of MSCs is important to take into account when MSCs are considered for clinical application. Our results suggest that the HLA background of MSCs and timing of MSC administration are important for the efficacy of MSC therapy.
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Meindert J
authors.initials: MJ
authors.lastname: Crop
authors.forename: Sander S
authors.initials: SS
authors.lastname: Korevaar
authors.forename: Ronella
authors.initials: R
authors.lastname: de Kuiper
authors.forename: Jan N M
authors.initials: JN
authors.lastname: IJzermans
authors.forename: Nicole M
authors.initials: NM
authors.lastname: van Besouw
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Willem
authors.initials: W
authors.lastname: Weimar
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Hoogduijn
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology*